Alterations in β-Cell Calcium Dynamics and Efficacy Outweigh Islet Mass Adaptation in Compensation of Insulin Resistance and Prediabetes Onset

• DOI: 10.2337/db15-1718
• Publication Date: 2016-04-09T04:04:34Z
• Authors: Chunguang Chen; Helena Chmelova; Christian M. Cohrs; Julie A. Chouinard; Stephan R. Jahn; Julia Stertmann; Ingo Uphues; Stephan Speier
• Keywords: Prediabetes; Insulin oscillation

Emerging insulin resistance is normally compensated by increased production of pancreatic β-cells, thereby maintaining normoglycemia. However, it unclear whether this achieved adaptation β-cell function, mass, or both. Most importantly, still unknown which these adaptive mechanisms fail when type 2 diabetes develops. We performed longitudinal in vivo imaging calcium dynamics and islet mass transplanted islets Langerhans throughout diet-induced progression from normal glucose homeostasis, through compensation resistance, to prediabetes. The results show that predominated alterations while only gradually expands. Hereby, functional mediated efficacy, involves Epac signaling. Prior prediabetes, function displays decreased stimulated dynamics, whereas continues increase prediabetes onset. Thus, our data reveal a predominant role with distinct contributions triggering amplifying pathway the processes preceding These findings support protection recovery as primary goals for prevention treatment provide insight into potential therapeutic targets.